Effects of intrathecal neostigmine, bupivacaine, and their combination on sympathetic nerve activity in rats.
BACKGROUND
Intrathecal injection of local anesthetic agents is associated frequently with hypotension. Conversely, intrathecal administration of neostigmine increases blood pressure by enhancing the accumulation of acetylcholine in the spinal cord. The current study examined directly the interaction of intrathecal injection of bupivacaine and neostigmine on splanchnic sympathetic efferent nerve activity.


METHODS
Experiments were performed in rats with intrathecal catheters implanted for the long-term. Rats were anesthetized with ketamine (40 mg/kg, intramuscularly) and alpha-chloralose (60 mg/kg, intraperitoneally). The skin incision sites were infiltrated with 1% lidocaine. Sympathetic efferent activity was recorded from the left greater splanchnic nerve. Sympathetic nerve activity was measured continuously before and after intrathecal injection of saline, 430 nmol (140 microg) of bupivacaine, 25 nmol (7.6 microg) of neostigmine, and a combination of bupivacaine and neostigmine all in volumes of 5 microl. Each group consisted of six animals.


RESULTS
Compared with baseline nerve activity, intrathecal injection of neostigmine increased splanchnic sympathetic nerve activity significantly by (mean +/- SEM) 112 +/- 29% after an onset latency of 6.8 +/- 0.9 min. In contrast, bupivacaine decreased splanchnic nerve activity significantly (-65 +/- 13%) after a latency of 3.3 +/- 0.5 min after intrathecal administration. Similar to the effect of saline, intrathecal coadministration of bupivacaine and neostigmine did not alter the splanchnic sympathetic nerve activity significantly.


CONCLUSIONS
The current study provides electrophysiologic evidence that intrathecal injection of neostigmine increases whereas bupivacaine decreases sympathetic nerve activity. Further, addition of neostigmine effectively counteracts the inhibitory effect of spinal bupivacaine on the sympathetic nerve activity.
Pan
H L
HL
Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA. hpan@bgsm.edu
Song
H K
HK
Eisenach
J C
JC
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D002045:Bupivacaine / Q000008:administration & dosage / Q000494:pharmacology*; D002800:Cholinesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004338:Drug Combinations; D004347:Drug Interactions; D004594:Electrophysiology; D007278:Injections, Spinal; D008297:Male; D009388:Neostigmine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013153:Splanchnic Nerves / Q000187:drug effects / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects*
D000779:Anesthetics, Local; D002800:Cholinesterase Inhibitors; D004338:Drug Combinations; D009388:Neostigmine; D002045:Bupivacaine